GABA enhances acetylcholine release from hippocampal nerve endings through a mechanism blocked by a GABA uptake inhibitor.

The effect of gamma-aminobutyric acid (GABA) on the release of [3H]acetylcholine [( 3H]ACh) was investigated using superfused rat hippocampal synaptosomes. GABA enhanced the basal efflux of [3H]ACh. The effect of GABA was bicuculline-insensitive. Muscimol, (+/-)-baclofen or (-)-baclofen did not increase [3H]ACh release. The effect of GABA was counteracted by SK&F 89976 A (N-(4,4-diphenyl-3-butenyl)-nipecotic acid), a GABA uptake inhibitor. One possible interpretation of the results is that a GABA transport system is present on cholinergic terminals, suggesting that GABA and ACh may coexist in some rat hippocampus nerve endings. Another possibility is that the effect of GABA is mediated by a novel subtype of GABA receptor sensitive to SK&F 89976 A.